Tumor necrosis factor receptor superfamily member 16 (TNFRSF16) (p75NTR)

The p75 neurotrophin receptor (p75NTR), officially known as Tumor necrosis factor receptor superfamily member 16 (TNFRSF16), is a versatile transmembrane protein that serves as a low-affinity receptor for all mature neurotrophins and a high-affinity receptor for their pro-forms [2.3.1, 2.3.2]. It plays a dual role in the nervous system, acting as a molecular switch that can trigger either cell survival and synaptic plasticity or programmed cell death and axonal degeneration, depending on the presence of specific ligands and co-receptors like Trk, sortilin, or Nogo [2.3.3, 3.3.1]. Beyond its neurotrophic functions, p75NTR (also known as CD271) is a critical marker for cancer stem cells in melanoma and head and neck cancers, where it contributes to tumor initiation, metastasis, and resistance to therapy [2.1.1, 2.1.2, 3.1.2]. In neurodegenerative diseases such as Alzheimer's and amyotrophic lateral sclerosis (ALS), the receptor is often upregulated or abnormally processed, making it a significant therapeutic target [2.2.1, 3.2.1]. Small molecule modulators like LM11A-31 are currently being investigated in clinical trials to shift p75NTR signaling toward neuroprotection by downregulating degenerative pathways [3.3.1, 3.4.1]. Additionally, targeted therapies in oncology aim to exploit its expression to eliminate resistant cancer cell populations through mechanisms like photoimmunotherapy [3.1.3, 3.1.4].

Other names

CD271Low-affinity nerve growth factor receptorLNGFRp75 neurotrophin receptorNGFRGp80-LNGFR

Modulation of signaling pathways to favor survival over apoptosis in neurodegeneration, or activation of the death domain to induce apoptosis in cancer cells [2.2.4, 3.1.1].